The objective of the proposed research is to increase our understanding of the regulation of gene expression in human cells through the study of spontaneous and induced mutants of diploid fibroblasts and lymphoblasts in culture. Mutants will be sought that have "turned on" or "induced" an enzyme in the arginine or cysteine pathways which is not normally expressed in these cells; also, revertants will be sought in cells from individuals with inborn errors of arginine or cysteine metabolism. After irradiation or treatment with chemical mutagens, mutants will be selected in arginine or cysteine-free medium supplemented with a precursor of that amino acid. Whenever possible, mutants will be characterized biochemically and genetically to ascertain the gene involved, its dominance in inter- and intraspecific hybrids and its chromosomal location. Analysis of these cells with altered control mechanisms should enhance our understanding of growth, both normal as in differentiation and abnormal as in cancer. BIBLIOGRAPHIC REFERENCES: Jacoby, L. B. and J. D. Irr. Acquisition of argininosuccinate synthetase in variant clones of human lymphoblasts. J. Cell Biol. 67:189a, 1975 (abstract). Jacoby, L. B. Canavanine-resistant variants of human lymphoblasts. J. Cell Biol. 70: 134a, 1976 (abstract).